Alden L. Gross is an Assistant Professor in the Department of Epidemiology at the Johns Hopkins Bloomberg School of Public Health. He seeks a mentored career development award to obtain critical knowledge skills in the biology of aging, particularly as it relates to frailty in older adults, and necessary research experience for an independent career as an epidemiologist in aging. The training application details a five year plan of formal and informal instruction in the physiological basis of frailty and aging consisting f mentored research by an established team of experts, coursework, seminars, guided study in frailty by mentors, collaborations in richly educational working groups, national and local meetings, and mentored research informed by the training. Short-term career goals include to complete coursework in the biology of aging and practice, disseminate high-quality mentored research through publications and presentations, engage in career development activities, and apply for independent R01 funding beginning in the fourth year of the award period. Long-term career goals are to be an independent psychiatric epidemiologist with content expertise in the biology of aging, particularly as it relates to frailty in older adults. The specific aims of the research proposed are to develop and validate an objective method for measuring physiological frailty using combinations of physiological markers of dysregulation across multiple body systems in an integrative data analysis of three longitudinal datasets, to determine whether physiological frailty or cognitive impairment predicts subsequent change in the other, and to evaluate reciprocal relationship between changes in physiological frailty and cognitive decline with attention to implications for future public health interventions. An ancillary study is proposd to enrich existing biomarker data. Completion of the proposed aims will provide preliminary findings that will lay the groundwork for mounting interventions to establish frailty as a window o opportunity for intervention or screening of subsequent cognitive decline.